EBV is the causative agent of lymphoproliferative disease-infectious mononucleosis (IM). It can also transform human lymphocytes in vitro. It has already been demonstrated that adult human T cells can suppress EBV infection of B cells. This function cannot be performed by fetal lymphocytes. The first objective of the proposed research will be to further elucidate the characteristics of the mechanism by which T cells suppress EBV infection. Experiments will be performed to study at what time during infection and transformation the T cells are active. The interaction of the T cell with the infected B cell will be studied. Specifically, requirements for cell-to-cell contact, mediation by soluble factors and restriction by HLA identity will be tested. The ontology of the response and the nature of the defect in fetal lymphocytes will be studied. The second objective will be to define the relevance of the in vitro studies to in vivo infection. The ability of T cells from patients in the acute phase of IM will be tested for their ability to suppress infection in vitro. The levels of activity will be compared to the course of the disease. These experiments should demonstrate whether or not the ability of T lymphocytes to suppress EBV infection of B cells in vitro constitutes a new form of immunity in humans and what relevance it has to recovery from lymphoproliferative disease.